Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3
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Yin-ling Xiu1, Kai-xuan Sun1, Xi Chen1, Shuo Chen2, Yang Zhao2, Qing-guo Guo1 and Zhi-Hong Zong1
1Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110122, China
2Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
Zhi-Hong Zong, email: [email protected]
Keywords: lncRNA, Meg3, autophagy, epithelial ovarian carcinoma, tumorigenesis and progression
Received: September 16, 2016 Accepted: February 14, 2017 Published: March 07, 2017
Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to be associated with the pathogenesis of multiple malignancies. However, little is known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this study, we found that the expression of Meg3 was lower in epithelial ovarian carcinoma, and has potential to be considered as a biomarker for ovarian cancer. After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3, phenotypic changes and autophagy-related molecules were examined. Upregulation of Meg3 inhibited cell proliferation, plate colony formation, induced cell cycle arrest in G2 phases, and promoted apoptosis. Observation of autophagosomes was performed by transmission electron microscopy. The expression levels of LC3-II, ATG3, LAMP1 were elevated, while SQSTM1/p62 expression declined. Upregulated expression of Meg3 also suppressed tumorigenesis in vivo in a xenograft mouse model through upregulating ATG3 expression. RIP (ribonucleoprotein immunoprecipitation) and RNA pull-down assays showed that Meg3 was co-immunoprecipitated with ATG3. In addition, Meg3 protected ATG3 mRNA from degradation following treatment with actinomycin D. Overall, our results suggest that the lncRNA Meg3 acts as a tumor suppressor in EOC by regulating ATG3 activity and inducing autophagy.
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